Oral care composition

ABSTRACT

Disclosed are oral care compositions, for example dentifrice compositions, comprising an oral care composition comprising an orally acceptable vehicle, metal oxide particles having an average particle size of no greater than a dentin tubule and at least one amino acid capable of chelating the metal oxide. The composition may comprise a polymeric adherent material for adhering the metal oxide particles in the dentin tubule. The metal oxide particles have a median particle size of 5 microns or less, and may comprise zinc oxide.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.13/637,370, filed on Sep. 26, 2012, which is a national stage entryunder 35 U.S.C. §371 of International Patent Application No.PCT/US2010/029472, filed on Mar. 31, 2010, which are both herebyincorporated by reference in their entireties.

The present invention relates to an oral care composition, for example adentifrice composition, for enhanced delivery of anantiplaque/anticalculus agent to the oral surfaces in the oral cavity,and which may additionally treat or prevent hypersensitivity of theteeth. The present invention also relates to a method of delivering anantiplaque/anticalculus agent to the oral surfaces in the oral cavityand simultaneously treating or preventing hypersensitivity of the teeth.The present invention has particular application in treating orpreventing hypersensitivity of the teeth by occluding dentin tubules.

BACKGROUND

Dentin is a portion of the tooth internal to the enamel and cementumthat has a radially striated appearance owing to a large number of finecanals or tubules known as the dentinal tubules. Tubules run from thepulp cavity to the periphery of the dentin and are generally about twomicrons in diameter at their base and somewhat narrower at theirperiphery. Tubules are not usually exposed to the environment in theoral cavity, as they are usually covered by enamel or cementum. Thecementum in turn is often covered by the gums.

It is commonly understood that partially or fully exposed tubules canlead to tooth sensitivity, an irritating and painful condition. In thistheory, recession of the gum line exposes cementum to erosion. Theeroded cementum in turn exposes the hollow dentinal tubules. The exposedtubules cause nerves within the tooth to be affected excessively byexternal oral stimuli because material and energy transfer between theexterior and interior of the tooth is accelerated through the tubules.Common environmental stimuli, such as heat, cold, chemicals and physicaland mechanical pressure or stimuli, such as brushing, are able toirritate the nerve through the open dentin tubules and thereby createpain. The pain of sensitive teeth appears to result from these stimuli,which apparently cause fluid movements in the dentinal tubules thatactivate pulpal nerve endings.

Conventionally, two approaches have been taken to treat or amelioratetooth sensitivity. Under one approach, the chemical environment proximalto the nerve is altered by application of various agents, such that thenerve is not stimulated, or not stimulated as greatly. Known agentsuseful in this chemical approach, including potassium salts (such aspotassium nitrate, potassium bicarbonate, potassium chloride) andstrontium, zinc salts, and chloride salts.

The second approach involves the mechanical shield of the nerve by,e.g., blocking of the dentinal tubules wholly or partially with “tubuleblocking agents.” Agents that have been disclosed in the prior artinclude, e.g., cationic alumina, clays, water-soluble or water-swellablepolyelectrolytes, oxalates, amorphous calcium phosphate, hydroxyapatite,maleic acid copolymers and polyethylene particles.

US-A1-2009/0186090 in the name of the present Applicant discloses theprovision of an oral care composition that reduces and/or eliminates theperception of tooth sensitivity. The composition includes an adherentmaterial and includes, in part, silica particles having a particle sizeof 2-5 microns.

However, even though such an oral care composition provides clinicalhypersensitivity relief, there is nevertheless still a need in the artfor an oral care composition, in particular a dentifrice, that, uponuse, provides enhanced prevention or reduction of tooth sensitivity andis not associated with significant processing or formulationdisadvantages.

It is also known is the art to use zinc oxide as anantiplaque/anticalculus agent. It is also known to use complexes ofdivalent or trivalent metal ions as antiplaque agents.

It has been demonstrated in the literature that the solubility of zinccan be improved by forming a complex with a chelating molecule such asethylenediamine tetraacetic acid or a bioactive molecule such as acyclic alpha-hydroxyketone. For example, as disclosed in U.S. Pat. No.6,287,541, specific cyclic alpha-hydroxyketones are used as complexingagents for divalent copper, zinc, iron or tin and trivalent iron S. Y.Gan, et al. “Antibacterial Activity of Zn-chelator Complexes.” IADR,March 2009 discloses the use of inert biocompatible chelators for zinc.

However, increased solubility does not guarantee an increase inanti-plaque, anti-gingivitis, hypersensitivity, and/or fresh breathefficacy. To provide these benefits the zinc must be delivered to thehard and/or soft tissues in the oral cavity.

There is still a need for enhanced delivery of antiplaque/anticalculusagents to the oral surfaces, in particular hard and/or soft tissue inthe oral cavity.

SUMMARY

In some embodiments, the present invention provides an oral carecomposition comprising an orally acceptable vehicle, a source of metaloxide particles having an average particle size of no greater than adentin tubule and at least one amino acid. In some embodiments, at leastone of said one or more amino acids is capable of chelating the metaloxide particles.

In some embodiments, the metal oxide particles may have an averageparticle size of from 1 to 7 microns. In some embodiments, the metaloxide particles have an average particle size of 5 microns or less.

The metal oxide typically comprises at least one metal oxide selectedfrom zinc oxide, stannous oxide, titanium oxide, calcium oxide, copperoxide and iron oxide or a mixture thereof.

In other embodiments, the metal oxide is zinc oxide.

The metal oxide particles may have a particle size distribution of 3 to4 microns, a particle size distribution of 5 to 7 microns, a particlesize distribution of 3 to 5 microns, a particle size distribution of 2to 5 microns, or a particle size distribution of 2 to 4 microns.

The metal oxide particles may be present in an amount of up to 5% byweight, based on the total weight of the oral care composition, forexample in an amount of from 0.5 to 2% by weight, being based on thetotal weight of the oral care composition.

The metal oxide may be incorporated into the oral care composition in atleast one form selected from a powder, a nanoparticle solution orsuspension, or encapsulated in a polymer or bead.

Preferably, the at least one amino acid is selected from arginine,L-arginine, cysteine, leucine, isoleucine, lysine, L-lysine, alanine,asparagine, aspartate, phenylalanine, glutamate, glutamic acid,threonine, glutamine, tryptophan, glycine, valine, proline, serine,tyrosine, and histidine, and mixtures thereof.

Typically, the at least one amino acid is selected from L-arginine,cysteine, isoleucine, L-lysine, glutamic acid, serine, and mixturesthereof.

More typically, the at least one amino acid comprises L-arginine.

Optionally, the at least one amino acid is present in an amount of up to5% by weight, further optionally from 0.5 to 5% by weight, still furtheroptionally from 2.5 to 4.5% by weight, based on the total weight of theoral care composition.

The oral care composition may further comprise a polymeric adherentmaterial for adhering the metal oxide particles in the dentin tubule.

In some embodiments, the metal oxide is encapsulated in a polymericadherent material.

In some embodiments, the polymeric adherent material, comprises at leastone cellulose polymer.

The at least one cellulose polymer may be one or more hydroxyalkylcellulose polymer selected from hydroxypropylmethyl cellulose (HPMC),hydroxyethylpropyl cellulose (HEPC) hydroxybutylmethyl cellulose (HBMC),and carboxymethyl cellulose (CMC).

Typically, the polymeric adherent material comprises a mixture of twohydroxyalkyl cellulose polymers having different molecular weight andthe metal oxide comprises zinc oxide which is encapsulated in themixture of two hydroxyalkyl cellulose polymers.

In other embodiments, the polymeric adherent material comprises at leastone polymer selected from include poly(ethylene oxide) polymers, linearpolyvinylpyrrolidone (PVP) and cross-linked polyvinylpyrrolidone (PVP),polyethylene glycol (PEG)/polypropylene glycol (PPG) copolymer, ethyleneoxide (EO)-propylene oxide (PO) block copolymers, ester gum, shellac,pressure sensitive silicone adhesives, methacrylates or mixturesthereof.

Preferably, the oral care composition is a dentifrice composition, suchas a toothpaste or a gel.

Alternatively, the oral care composition is formulated into a formselected from a mouth rinse, a gum, a dissolvable lozenge, and adissolvable film.

The present invention further provides a method of reducing dentalsensitivity comprising applying to the surface of a mammalian tooth anoral care composition of the present invention.

The present invention yet further provides a method of protecting dentalsurfaces from acid-mediated degradation, comprising applying to thesurface of a mammalian tooth an oral care composition of the presentinvention.

The present invention still further provides a method of maintaining orincreasing the systemic health of a mammal comprising applying acomposition to an oral surface of a mammal at least once a day for aduration of time, wherein the composition comprises:

-   a. an oral care composition of the present invention, and-   b. an agent selected from triclosan; triclosan monophosphate;    chlorhexidine; alexidine; hexetidine; sanguinarine; benzalkonium    chloride; salicylanilide; domiphen bromide; cetylpyridinium chloride    (CPC); tetradecylpyridinium chloride (TPC);    N-tetradecyl-4ethylpyridinium chloride (TDEPC); octenidine;    delmopinol; octapinol; nisin; zinc ion agent; copper ion agent;    essential oils; furanones; bacteriocins ethyllauroyl arginate,    extracts of magnolia, a metal ion source, fluoride, stannous ions,    arginine bicarbonate, honokiol, magonol, ursolic acid, ursic acid,    morin, extract of sea buckthorn, a peroxide, an enzyme, a Camellia    extract, a flavonoid, a flavan, halogenated diphenyl ether,    creative, and propolis.

The present invention also provides a method of occluding a dentintubule within the surface of a mammalian tooth comprising applying tothe tooth surface a composition according to the present invention.

The compositions may contain additional therapeutic and non-therapeuticcomponents, and may also be utilized in the practice of various methods,all of which are included within the scope of the invention. Thecomposition and methods within the scope of the invention may be usefulin, for example, reducing or eliminating tooth sensitivity of a mammal,improving/maintaining systemic health, and/or occluding dentin tubules.

The present invention is predicated on the finding by the presentinventors that charged amino acids and peptides have an affinity for thesoft and/or hard tissue in the oral cavity and are also capable ofchelating a metal oxide, such as zinc oxide, stannous oxide, or copperoxide, which has antiplaque/anticalculus efficacy when present in atherapeutically effective amount. Upon introduction of such a complexinto the oral cavity, for example by brushing of the teeth, the aminoacid/peptide can act to deliver the metal oxide to the desired locationin the mouth. For example, if zinc oxide is delivered to dentin, thezinc oxide amino acid complex can occlude dentin tubules and providehypersensitivity relief. Yet further the metal oxide can provideantiplaque/anticalculus treatment or prevention.

The present inventors have found in particular that the deliver of zincoxide from dentifrice to a hydroxyapatite surface can be increased withthe addition of an amino acid such as L-arginine. The form of the zincoxide in the dentifrice can include, but is not limited to, powder,nanoparticle solution, and encapsulation of the zinc oxide by a polymerfilm or bead.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a comparison of the occlusion incidence resulting fromtreating a mammalian tooth dentin substrate with an Example of an oralcare composition of the invention versus a Comparative Example, thesubstrates being shown untreated, after treatment by brushing, and aftertreatment by a first acid challenge.

DETAILED DESCRIPTION

It should be understood that the detailed description and specificexamples, while indicating embodiments of the invention, are intendedfor purposes of illustration only and are not intended to limit thescope of the invention.

The following definitions and non-limiting guidelines must be consideredin reviewing the description of this invention set forth herein. Theheadings (such as “Background of the Invention” and “Summary,”) andsub-headings (such as “Compositions”) used herein are intended only forgeneral organization of topics within the disclosure of the invention,and are not intended to limit the disclosure of the invention or anyaspect thereof. In particular, subject matter disclosed in the“Background of the Invention” may include aspects of technology withinthe scope of the invention, and may not constitute a recitation of priorart. Subject matter disclosed in the “Summary” is not an exhaustive orcomplete disclosure of the entire scope of the invention or anyembodiments thereof. Classification or discussion of a material within asection of this specification as having a particular utility (e.g., asbeing an “active” or a “carrier” ingredient) is made for convenience,and no inference should be drawn that the material must necessarily orsolely function in accordance with its classification herein when it isused in any given composition.

The citation of references herein does not constitute an admission thatthose references are prior art or have any relevance to thepatentability of the invention disclosed herein. Any discussion of thecontent of references cited in the Background of the Invention isintended merely to provide a general summary of assertions made by theauthors of the references, and does not constitute an admission as tothe accuracy of the content of such references. Each and every referencecited herein is hereby incorporated by reference in its entirety.

The description and specific examples, while indicating embodiments ofthe invention, are intended for purposes of illustration only and arenot intended to limit the scope of the invention. Moreover, recitationof multiple embodiments having stated features is not intended toexclude other embodiments having additional features, or otherembodiments incorporating different combinations the stated of features.Specific Examples are provided for illustrative purposes of how to makeand use the compositions and methods of this invention and, unlessexplicitly stated otherwise, are not intended to be a representationthat given embodiments of this invention have, or have not, been made ortested.

As used herein, the words “preferred” and “preferably” refer toembodiments of the invention that afford certain benefits under certaincircumstances. However, other embodiments may also be preferred, underthe same or other circumstances. Furthermore, the recitation of one ormore preferred embodiments does not imply that other embodiments are notuseful, and is not intended to exclude other embodiments from the scopeof the invention. In addition, the compositions and the methods maycomprise, consist essentially of, or consist of the elements describedtherein.

As used herein, the word “include,” and its variants, is intended to benon-limiting, such that recitation of items in a list is not to theexclusion of other like items that may also be useful in the materials,compositions, devices, and methods of this invention.

As used herein, the term “about,” when applied to the value for aparameter of a composition or method of this invention, indicates thatthe calculation or the measurement of the value allows some slightimprecision without having a substantial effect on the chemical orphysical attributes of the composition or method. If, for some reason,the imprecision provided by “about” is not otherwise understood in theart with this ordinary meaning, then “about” as used herein indicates apossible variation of up to 5% in the value.

As referred to herein, all compositional percentages are by weight ofthe total composition, unless otherwise specified.

The invention described herein includes an oral care composition thatcontains at least (a) an amino acid and (b) a metal oxide particle. Themetal oxide particle may have an average particle size of no greaterthan a dentin tubule, or alternatively it may have a median particlesize of 5 microns or less.

In some embodiments, the oral care composition comprises at least oneamino acid capable of chelating the metal oxide. The at least one aminoacid may be selected from arginine, L-arginine, cysteine, leucine,isoleucine, lysine, L-lysine, alanine, asparagine, aspartate,phenylalanine, glutamate, glutamic acid, threonine, glutamine,tryptophan, glycine, valine, praline, serine, tyrosine, and histidine,and mixtures thereof.

Typically, the at least one amino acid is selected from L-arginine,cysteine, isoleucine, L-lysine, glutamic acid, serine, and mixturesthereof.

More typically, the at least one amino acid comprises L-arginine.

The at least one amino acid is present in an amount sufficienteffectively to chelate the metal oxide, and typically may be present inan amount of up to 5% by weight, further optionally from 0.5 to 5% byweight, still further optionally from 25 to 43% by weight, based on thetotal weight of the oral care composition.

Metal Oxide Particles

The metal oxide particles may be present in an amount of up to 5% byweight, preferably of up to 2% by weight, more preferably from 0.5 to 2%by weight, still more preferably from 1 to 2% by weight, the weightbeing based on the total weight of the oral care composition.

The metal oxide may comprise one or more metal oxides selected from zincoxide, stannous oxide, titanium oxide, calcium oxide, copper oxide andiron oxide. Mixtures of such metal oxides may be used. However, zincoxide is most preferred. Zinc oxide is known in the art to act as anantiplaque and anticalculus agent when used in oral care compositions.Accordingly, when zinc oxide is used in the oral care compositions ofpreferred embodiments of the present invention, the zinc oxide mayexhibit a dual function, namely occlusion of dentin tubules andproviding an antiplaque/anticalculus effect.

In some embodiments, the source of metal oxide particles is selectedfrom a powder, a nanoparticle solution or suspension, a capsule and abead.

Therefore the embodiments of the invention include metal oxide,preferably zinc oxide, particles of a particular particle size, theparticle size being selected to achieve occlusion of dentin particles.

Particle Size and Distribution

In this specification, particle size distribution was measured using aMalvern Particle Size Analyzer, Model Mastersizer 2000 (or comparablemodel) (Malvern Instruments, Inc. Southborough, Mass.), wherein ahelium-neon gas laser beam is projected through as transparent cellwhich contains silica, such as, for example, silica hydrogel particlessuspended in an aqueous solution. Light rays which strike the particlesare scattered through angles which are inversely proportional to theparticle size. The photodetector arrant measures the quantity of lightat several predetermined angles. Electrical signals proportional to themeasured light flux values are then processed by a microcomputer system,against a scatter pattern predicted from theoretical particles asdefined by the refractive indices of the sample and aqueous dispersantto determine the particle size distribution of the metal oxide. It willbe understood that other methods of measuring particle size are known inthe art, and based on the disclosure set forth herein, the skilledartisan will understand how to calculate median particle size, meanparticle size, and/or particle size distribution of metal oxideparticles of the present invention.

In an aspect, suitable metal oxide particles such as zinc oxideparticles for oral care compositions of the invention have, for example,a particle size distribution of 3 to 4 microns, or alternatively, aparticle size distribution of 5 to 7 microns, alternatively, a particlesize distribution of 3 to 5 microns, alternatively, a particle sizedistribution of 2 to 5 microns, or alternatively, a particle sizedistribution of 2 to 4 microns.

The oral compositions within the scope of the invention include metaloxide particles such as zinc oxide that have a median particle size thatis no greater than the average diameter of a mammalian dentin tubule,such that one or more particles is/are capable of becoming lodged withinthe tubule, thereby effecting a reduction or elimination of perceivedtooth sensitivity. Suitable particles may have, for example, a medianparticle size of 8 microns or less, alternatively, a median particlesize of 3 to 4 microns, alternatively, a median particle size of 5 to 7microns, alternatively, a median particle size of 3 to 5 microns,alternatively, a median particle size of 2 to 5 microns, oralternatively, a median particle size of 2 to 4 microns.

In an aspect of the invention, the metal oxide particles such as zincoxide have a particle size which is a median particle size. In anotheraspect, that particle size is an average (mean) particle size. In anembodiment, the mean particle comprises at least 5%, at least 10%, atleast 15%, at least 20%, at least 25%, at least 30%, at least 35%, or atleast 40% of the total metal oxide particles in an oral care compositionof the invention.

In an aspect of the invention, the metal oxide particles such as zincoxide have a particle size characterized by the parameters of a medianparticle size of about 2 μm to about 4 μm, a d10 of about 0.5 μm toabout 2 μm, and a d90 of about 5 μm to about 10 μm. As used herein, d10refers to particles having a diameter that is 10% of the threshold ofthe sampled population (i.e., 10% of the population is equal to orsmaller than the d10 value), and d90 refers to particles having adiameter that is 90% of the threshold of the sampled population (i.e.,90% of the population is equal to or smaller than the d90 value). Inanother aspect, a metal oxide such as zinc oxide has a particle sizecharacterized by a median particle size of about 3 μm to about 5 μm, ad10 of about 1.5 μm to about 3 μm, and a d90 of about 6 μm to about 11μm.

The metal oxide particle may be prepared by any means known or to bedeveloped in the art, and may be surface modified, if desired, toincrease the capacity of the particle to adhere to a tooth surface.

Abrasive Particulates

The oral compositions may further comprise, in addition to the metaloxide dentin tubule-occluding particles, one or more abrasiveparticulates. Any abrasive particulates may be used and may be selectedfrom sodium bicarbonate, calcium phosphate (e.g., dicalcium phosphatedihydrate), calcium sulfate, precipitated calcium carbonate, silica(e.g., hydrated silica), iron oxide, aluminium oxide, perlite, plasticparticles, e.g., polyethylene, and combinations thereof. In particular,the abrasive may be selected from a calcium phosphate (e.g., dicalciumphosphate dihydrate), calcium sulfate, precipitated calcium carbonate,silica (e.g., hydrated silica), calcium pyrophosphate and combinations.Any type of silica may be used, such as precipitated silicas or silicagels.

In an embodiment, the oral care composition comprises a silica that hasa particle size and an amount and distribution in the oral carecomposition so that the silica has a dual function, and functions notonly as a dentin tubule-occluding particulate but also as an abrasiveparticulate. Such a dual function particulate ma be provided by acommercially available silica such as INEOS AC43, available in commercefrom Ineos Silicas, Warrington, United Kingdom, as described elsewhereherein. In an embodiment, such a silica has a median particle size from3 μm to 5 μm, as described in detail elsewhere herein.

Various abrasives may be used in accordance with the present invention.One class of abrasives comprises silica particles as set forth in detailherein. Another class of abrasives are powdered silicas, particularly,silica xerogels as defined in U.S. Pat. No. 3,538,230. Additionally, asset forth in U.S. Pat. No. 4,358,437, powdered forms of calciumcarbonate in an abrasive form is another class of abrasives.

The compositions of the present invention may further comprise anoptional abrasive useful for example as a polishing agent. Any orallyacceptable abrasive can be used, but type, fineness, (particle size) andamount of abrasive Should be selected so that tooth enamel is notexcessively abraded in normal use of the composition. Suitable optionalabrasives include silica, for example in the form of precipitated silicaor as admixed with alumina, insoluble phosphates, calcium carbonate, andmixtures thereof. Among insoluble phosphates useful as abrasives areorthophosphates, polymetaphosphates and pyrophosphates. Illustrativeexamples are dicalcium orthophosphate dihydrate, calcium pyrophosphate,calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphateand insoluble sodium polymetaphosphate.

Polymers and Adherent Materials

The oral compositions of the invention may also include a polymericadherent material. The polymer can assist in the retention of the metaloxide particles within the dentin tubules under salivary flow and duringexposure to acidic foods and beverages.

The polymeric adherent material may be any known or to be developed inthe art that attaches to the surface of a mammalian tooth and/or to theheterogeneous biofilm which also may be present on a tooth's surface.Attachment may occur by any means, such as ionic interaction, van derWaals forces, hydrophobic-hydrophilic interactions, etc. The adherentmaterial may be, for example, any homopolymers or copolymers(hereinafter referred to collectively as a “polymers”) that adhere tothe surface of a tooth. Such polymers may include cellulose polymers,for example one or more hydroxyalkyl cellulose polymers, such ashydroxypropylmethyl cellulose (HPMC), hydroxyethylpropyl cellulose(HEPC), hydroxybutylmethyl cellulose (HBMC), carboxymethyl cellulose(CMC).

In one embodiment the polymeric adherent material comprises a mixture ofcellulose materials, for example a mixture of two hydroxyalkyl cellulosematerials having different molecular weight. The mixture typicallycomprises a mixture of two hydroxypropyl methyl cellulose materials ofdifferent molecular weight. In a particularly preferred embodiment, thetwo hydroxypropyl methyl cellulose materials comprise a mixture of HPMCmaterials available commercially from the Dow Chemical Company under thetrade designation Methocel E5 and Methocel E50.

Modifying the polymer system can increase the strength of the filmmatrix to support a high loading of solids, especially zinc oxide. Byrebalancing the polymer system, the present inventors discovered amethod in which more actives can be loaded into the film than could bedone previously. This creates a film with a higher concentration of zinccompound that can be delivered, and also reduces the amount of filmneeded to deliver these higher amounts. The improved higher loadingzinc-containing film formula provides higher deposition onto surfacesfor superior efficacy. Also, improving the film formulation to hold ahigher loading of zinc compound can reduce the amount of total filmneeded in a product, while at the same time, delivering the sameefficacy as with a lower loading of film.

The polymers may alternatively or additionally include poly(ethyleneoxide) polymers (such as POLYOX from Dow Chemical), linear PVP andcross-linked PVP, PEG/PPG copolymers (such as BASF Pluracare L1220),ethylene oxide (EO)-propylene oxide (PO) block copolymers (such aspolymers sold under the trade mark Pluronic available from BASFCorporation), ester gum, shellac, pressure sensitive silicone adhesives(such as BioPSA from Dow-Corning), methacrylates, or mixtures thereof.In an embodiment, a copolymer comprises (PVM/MA). In an embodiment, acopolymer comprises poly(methylvinylether/maleic anhydride). In anotherembodiment, a copolymer comprises poly(methylvinylether/maleic acid). Inanother embodiment, a copolymer comprises poly(methylvinylether/maleicacid) half esters. In another embodiment, a copolymer comprisespoly(methylvinylether/maleic acid) mixed salts.

Polymers of any molecular weight may be used, including, for examplemolecular weights of 50,000 to 500,000, 500,000 to 2,500,000 or2,500,000 to 10,000,000 (calculated by either number average or weightaverage).

In an embodiment, a copolymer of methyl vinyl ether and maleic anhydridemay be used at a monomer ratio of from 1:4 to 4:1. Other polymers thatmay be used as adherent materials include those recited inUS-A1-2006/0024246, the contents of which are incorporated herein byreference.

Commercially-available polymers may be used in the present invention. Itis understood that over time, the exact size, weight and/or compositionof a commercially available polymer may change. Based on the disclosureset forth herein, the skilled artisan will understand how to determinewhether such polymers are useful in the invention

Compositions

In an aspect of the invention, metal oxide particle-containing oral carecompositions, which may optionally contain silica particles, candesensitize a tooth. In another aspect, such compositions of theinvention provide tooth desensitization that is superior to conventionaldesensitizing dentifrices. By way of a non-limiting example, a metaloxide particle-containing dentifrice of the invention provides toothdesensitization by providing a greater desensitization than aconventional dentifrice or a conventional desensitizing dentifrice, byproviding desensitization more rapidly than a conventional dentifrice ora conventional desensitizing dentifrice, or by a combination of greaterdesensitization and more rapid desensitization, among other effects. Inan embodiment, a metal oxide particle-containing composition of theinvention provides desensitization and/or superior desensitization inthe absence of any other desensitizing agent. In another embodiment, ametal oxide particle-containing composition of the invention providesdesensitization and/or superior desensitization, and may contain one ormore additional desensitizing agents, such as silica particles, asdescribed elsewhere herein.

The invention also encompasses methods of use and/or application of ametal oxide particle-containing desensitizing composition, which mayoptionally contain silica particles. In an embodiment, such a metaloxide particle-containing composition may be applied to the tooth viaconventional brushing techniques (e.g., use of a toothbrush). In anotherembodiment, such a metal oxide particle-containing composition may beapplied to the tooth via a method other than conventional brushingtechniques. Other methods of application include manual application(e.g., applying a composition to a tooth using one or more fingers,rubbing onto the tooth surface, rubbing in a circular motion, etc. . . .), or application using any known dental appliance or applicator. Itwill be understood, based on the disclosure set forth herein, that anymethod of smearing a composition onto a tooth, optionally using varyingdegrees of physical pressure, is encompassed by the invention.

Desensitization of a tooth according to the invention may be measured byany technique set forth herein, or any technique known to the skilledartisan.

Application of the composition to the tooth surface results in theintroduction of the composition into one or more dentin tubules. Thecomposition is applied to the teeth by any method set forth herein orknown in the art.

In some embodiments, the oral care composition may include any othertherapeutic, cosmetic, and/or aesthetic materials as may be desired.Examples include non-silica desensitizing agents (e.g. a nitrate salt,an arginine ester, a bicarbonate salt, potassium nitrate, anarginine-bicarbonate-phytate complex, potassium citrate, and arginine,among others), a chemical whitening agent (such as a peroxide releasingcompound), an opaque whitening agent (such as hydroxyapatite) and ananticalculus agent. Other options for inclusion in the oral carecomposition of the invention include triclosan; stannous ion agents;chlorhexidine; alexidine; hexetidine; sanguinarine; benzalkoniumchloride; salicylanilide; domiphen bromide; cetylpyridinium chloride(CPC); tetradecylpyridinium chloride (TPC);N-tetradecyl-4-ethylpyridinium chloride (TDEPC); octenidine; delmopinol;octapinol; nisin; zinc ion agents; copper ion agents; essential oils;furanones; bacteriocins, ethyl lauroyl arginate, extracts of magnolia, ametal ion source, arginine bicarbonate, honokiol, magonol, ursolic acid,ursic acid, morin, extract of sea buckthorn, an enzyme, a Camelliaextract, a flavonoid, a flavan, halogenated diphenyl ether, creatine,and propolis.

The oral care composition may in particular be a dentifrice compositionwhich may be a toothpaste or a gel.

The composition according to the present invention may comprise anantimicrobial agent which may be selected from halogenated diphenylether (triclosan), herbal extracts or essential oils (e.g., rosemaryextract, thymol, menthol, eucalyptol, methyl salicylate), bisguanideantiseptics (e.g., chlorhexidine, alexidine, or octenidine), phenolicantiseptics, hexetidine, povidone iodine, delmopinol, salifluor,sanguinarine, propolis, oxygenating agents (e.g., hydrogen peroxide,buffered sodium peroxyborate, or peroxycarbonate), cetyl pyridiniumchloride, magnolia extract, magnolol, honokiol, butyl magnolol, propylhonokiol, and mixtures thereof. Anti-attachment agents such as Solrolalso can be included, as well as plaque dispersing agents such asenzymes (papain, glucoamylase, etc.).

The composition according to the present invention may also comprise oneor more further agents typically selected from an anti-plaque agent, awhitening agent, antibacterial agent, cleaning agent, a flavouringagent, a sweetening agent, adhesion agents, surfactants, foammodulators, abrasives, pH modifying agents, humectants, mouth feelagents, colorants, abrasive, tartar control (anticalculus) agent,fluoride ion source, saliva stimulating agent, nutrient and combinationsthereof. Various components that may be added to the compositioninclude, for example, a sweetening agent such as saccharin, or sodiumsaccharin, alcohols such as ethanol, fluoride ion sources such as sodiumfluoride, as well as glycerine, sorbitol, propylene glycol, polyethyleneglycols, Poloxomer polymers such as POLOXOMER 407, PLURONIC F108, (bothavailable from BASF Corporation), alkyl polyglycoside (APG),polysorbate, PEG40, castor oil, menthol, and the like.

Flavorants among those useful herein include any material or mixture ofmaterials operable to enhance the taste of the composition. Any orallyacceptable natural or synthetic flavorant can be used, such as flavoringoils, flavoring aldehydes, esters, alcohols, similar materials, andcombinations thereof. Flavorants include vanillin, sage, marjoram,parsley oil, spearmint oil, cinnamon oil, oil of wintergreen(methylsalicylate), peppermint oil, clove oil, bay oil, anise oil,eucalyptus oil, citrus oils, fruit oils and essences including thosederived from lemon, orange, lime, grapefruit, apricot, banana, grape,apple, strawberry, cherry, pineapple, etc., bean- and nut-derivedflavors such as coffee, cocoa, cola, peanut, almond, etc., adsorbed andencapsulated flavorants and mixtures thereof. Also encompassed withinflavorants herein are ingredients that provide fragrance and/or othersensory effect in the mouth, including cooling or warming effects. Suchingredients include menthol, menthyl acetate, menthyl lactate, camphor,eucalyptus oil, eucalyptol, anethole, eugenol, cassia, oxanone,[alpha]-irisone, propenyl guaiethol, thymol, linalool, benzaldehyde,cinnamaldehyde, N-ethyl-p-menthan-3-carboxamine,N,2,3-trimethyl-2-isopropylbutanamide, 3-1-menthoxypropane-1,2-diol,cinnamaldehyde glycerol acetal (CGA), methane glycerol acetal (MGA), andmixtures thereof. One or more flavorants are optionally present in atotal amount of about 0.01% to about 5%, optionally in variousembodiments from about 0.05 to about 2%, from about 0.1% to about 2.5%,and from about 01 to about 0.5%.

Sweetening agents among those useful herein include dextrose,polydextrose, sucrose, maltose, dextrin, dried invert sugar, mannose,xylose, ribose, fructose, levulose, galactose, corn syrup, partiallyhydrolyzed starch, hydrogenated starch hydrolysate, sorbitol, mannitol,xylitol, maltitol, isomalt, aspartame, neotame, saccharin and saltsthereof, sucralose, dipeptide-based intense sweeteners, cyclamates,dihydrochalcones, and mixtures thereof.

Mouth-feel agents include materials imparting a desirable texture orother feeling during use of the composition.

Colorants among those useful herein include pigments, dyes, lakes andagents imparting a particular luster or reflectivity such as pearlingagents. In various embodiments, colorants are operable to provide awhite or light-colored coating on a dental surface, to act as anindicator of locations on a dental surface that have been effectivelycontacted by the composition, and/or to modify appearance, in particularcolor and/or opacity, of the composition to enhance attractiveness tothe consumer. Any orally acceptable colorant can be used, including FD&Cdyes and pigments, talc, mica, magnesium carbonate, calcium carbonate,magnesium silicate, magnesium aluminum silicate, silica, titaniumdioxide, zinc oxide, red, yellow, brown and black iron oxides, ferricammonium ferrocyanide, manganese violet, ultramarine, titaniated mica,bismuth oxychloride and mixtures thereof. One or more colorants areoptionally present in a total amount of about 0.001% to about 20%, forexample about 0.01% to about 10% or about 0.1% to about 5%.

The compositions of the present invention optionally comprise a tartarcontrol (anticalculus) agent. Tartar control agents among those usefulherein include salts of any of these agents, for example their alkalimetal and ammonium salts: phosphates and polyphosphates (for examplepyrophosphates), polyaminopropanesulfonic acid (AMPS), polyolefinsulfonates polyolefin phosphates, diphosphonates such asazacycloalkane-2,2-diphosphonates (e.g.,azacycloheptane-2,2-diphosphonic acid), N-methylazacyclopentane-2,3-diphosphonic acid, ethane-1-hydroxy-1,1-diphosphonicacid (EHDP) and ethane-1-amino-1,1-diphosphonate, phosphonoalkanecarboxylic acids and. Useful inorganic phosphate and polyphosphate saltsinclude monobasic, dibasic and tribasic sodium phosphates, sodiumtripolyphosphate, tetrapolyphosphate, mono-, di-, tri- and tetrasodiumpyrophosphates, sodium trimetaphosphate, sodium hexametaphosphate andmixtures thereof.

The compositions of the present invention optionally comprise a fluorideion source and useful, for example, as an anti-caries agent. Any orallyacceptable particulated fluoride ion source can be used includingpotassium, sodium and ammonium fluorides and monofluorophosphates,stannous fluoride, indium fluoride, amine fluorides such as olaflur(N′-octadecyltrimethylendiamine-N,N,N′-tris(2-ethanol)-dihydrofluoride)and mixtures thereof. One or more fluoride ion sources are optionallypresent in an amount providing a clinically efficacious amount ofsoluble fluoride ion to the oral composition.

The compositions of the present invention optionally comprise a salivastimulating agent useful, for example, in amelioration of dry mouth. Anyorally acceptable saliva stimulating agent can be used including withoutlimitation food acids such as citric, lactic, malic, succinic, ascorbic,adipic, fumaric and tartaric acids, and mixtures thereof. One or moresaliva stimulating agents are optionally present in saliva stimulatingeffective total amount.

The compositions of the present invention optionally comprise anutrient. Suitable nutrients include vitamins, minerals, amino acids,and mixtures thereof. Vitamins include Vitamins C and D, thiamine,riboflavin, calcium pantothenate, niacin, folic acid, nicotinamide,pyridoxine, cyanocobalamin, para-aminobenzoic acid, bioflavonoids, andmixtures thereof. Nutritional supplements include amino acids (such asL-tryptophane L-lysine, methionine, threonine, levocarnitine andL-carnitine), lipotropics (such as choline, inositol, betaine, andlinoleic acid), and mixtures thereof.

The dentifrice composition according to the present invention comprisesan orally acceptable carrier in a product such as a toothpaste or a gel.As used herein, an“orally acceptable carrier” refers to a material orcombination of materials that are safe for use in the compositions ofthe present invention, commensurate with a reasonable benefit/riskratio.

Preferably, specific materials and compositions to be used in thisinvention are, accordingly, pharmaceutically- orcosmetically-acceptable, clinically effective, and/or clinicallyefficacious. As used herein, such a “pharmaceutically acceptable” or“cosmetically acceptable”, “clinically effective”, and/or “clinicallyefficacious” component is one that is suitable for use with humansand/or animals and is provided in an appropriate amount (a clinicallyefficacious amount) to provide the desired therapeutic, prophylactic,sensory, decorative, or cosmetic benefit without undue adverse sideeffects (such as toxicity, irritation, and allergic response)commensurate with a reasonable benefit/risk ratio.

The oral care compositions described herein may be formulated into anydelivery form that permits contact of the metal oxide particles and theamino acid, and when present the polymeric adherent material, to thetooth surface. For example, the compositions may be formulated into amouth rinse, a paste, a gel, a lozenge (dissolvable or chewable), aspray, a gum and a film (wholly or partially dissolvable, orindissoluble). The composition may contain any conventional excipientsor carriers, although these will vary depending on the dosage form ormeans of dosage selected. Excipients or carriers can include, forexample, humectants, colorants, flavorants, glycerin, sorbitol, xylitol,and/or propylene glycol, water or other solvents, gum bases, thickeningagents, surfactants, carrageenan (rich moss), xanthan gum and sodiumcarboxymethyl cellulose, starch, polyvinyl pyrrolidone, hydroxyethylpropyl cellulose, hydroxybutyl methyl cellulose, hydroxypropyl methylcellulose, and hydroxyethyl cellulose and amorphous silicas.

Surfactants may be included, if desired. Examples of suitablesurfactants include water-soluble salts of higher fatty acidmonoglyceride monosulfates, such as the sodium salt of monosulfatedmonoglyceride of hydrogenated coconut oil fatty acids; higher alkylsulfates such as sodium lauryl sulfate; alkyl aryl sulfonates such assodium dodecyl benzene sulfonate; higher alkyl sulfoacetates, such assodium lauryl sulfoacetate; higher fatty acid esters of1,2-dihydroxypropane sulfonate; and the substantially saturated higheraliphatic acyl amides of lower aliphatic amino carboxylic compounds,such as those having 12-16 carbons in the fatty acid, alkyl or acylradicals; and the like. Examples of the last mentioned amides includeN-lauryl sarcosine, and the sodium, potassium and ethanolamine salts ofN-lauryl, N-myristoyl, or N-palmitoylsarcosine. Others include, forexample, nonanionic polyoxyethylene surfactants, such as Polyoxamer 407,Steareth 30, Polysorbate 20, and castor oil; and amphoteric surfactants,such as cocamidopropyl betaine (tegobaine), and cocamidopropyl betainelauryl glucoside; condensation products of ethylene oxide with varioushydrogen containing compounds that are reactive therewith and have longhydrocarbon chains (e.g., aliphatic chains of from 12 to 20 carbonatoms), which condensation products (ethoxamers) contain hydrophilicpolyoxyethylene moieties, such as condensation products of poly(ethyleneoxide) with fatty acids, fatty, alcohols, fatty amides and other fattymoieties, and with propylene oxide and polypropylene oxides.

In an embodiment, the oral composition includes a surfactant system thatis sodium laurel sulfate (SLS) and cocamidopropyl betaine.

The oral care composition of the invention may be prepared by any meansknown in the art. For example, preparation methods for dentifrices arewell known, for example, as described in U.S. Pat. No. 3,966,863; U.S.Pat. No. 3,980,767; U.S. Pat. No. 4,328,205; and U.S. Pat. No.4,358,437, the contents of which are incorporated herein by reference.In general, any humectant (e.g., glycerin, sorbitol, propylene glycol,and/or polyethylene glycol) is dispersed in water in a conventionalmixer under agitation. Into that dispersion are added the thickeners,such as carboxylmethyl cellulose (CMC), carrageenan, or xanthan gum; anyanionic polycarboxylate; any salts, such as sodium fluoride anticariesagents; and any sweeteners.

The resultant mixture is agitated until a homogeneous gel phase isformed. Into the gel phase are added any pigments utilized, such asTiO₂, and additionally any acid or base required to adjust the pH of thecomposition. These ingredients are mixed until a homogeneous phase isobtained.

The mixture is then transferred to a high speed/vacuum mixer, whereinthe surfactant ingredients are added to the mixture. The metal oxideparticles and any silica particles utilized are added subsequently. Anywater insoluble agents, such as triclosan, are solubilized in the flavoroils to be included in the dentifrice, and that solution is added alongwith the surfactants to the mixture, which is then mixed at high speedin the range from 5 to 30 minutes, under a vacuum of 20 to 50 mm of Hg.The resultant product is a homogeneous, semi-solid, extrudable paste orgel product.

Methods of Use

The oral care, e.g. dentifrice, composition according to the presentinvention may be administered to or applied to a human or other animalsubject. The composition is suitable for administration or applicationto the oral cavity of a human or animal subject.

The invention also includes within its scope several related methods.For example, the invention includes within its scope methods of reducingand methods of occluding a dentin tubule of a mammalian tooth, methodsof protecting dentin from acid-mediated degradation, and methods ofreducing dental sensitivity.

Each of these methods includes the steps of applying any of thecompositions described above to the tooth surface. Application may becarried out by any method, so long as the adherent material and theparticles are placed in contact with the tooth surface. Application maybe accomplished by brushing, flossing, prophylaxis, irrigating, wiping,rinsing (lavage of oral cavity), foam/gel and in-tray application,masticating, spraying, painting, etc., or applied by film or strip.

Dental sensitivity may be reduced according to a method of the inventionby applying a composition of the invention to a tooth surface. Acomposition may be applied using a traditional method, as described indetail elsewhere herein, or by any appliance or applicator, whether ornot typically associated with dental use. In an embodiment, one or morehuman fingers is used to apply a dental sensitivity-reducing compositionto one or more teeth. A finger can be used to smear the composition onthe surface of a tooth, or to otherwise apply the composition to thesurface of a tooth.

Alternatively, the invention includes methods to increase or maintainthe systemic health of a mammal by applying a composite to an oralsurface (both hard and soft tissues of the oral cavity). The compositionfor use in this method ma be any described above, provided that itcontains at least one of triclosan; triclosan monophosphate;chlorhexidine; alexidine; hexetidine; sanguinarine; benzalkoniumchloride; salicylanilide; domiphen bromide; cetylpyridinium chloride(CPC); tetradecylpyridinium chloride (TPC);N-tetradecyl-4-ethylpyridinium chloride (TDEPC); octenidine; delmopinol;octapinol; nisin; zinc ion agent; copper ion agent; essential oils;furanones; bacteriocins, ethyl lauroyl arginate, extracts of magnolia, ametal ion source, arginine bicarbonate, honokiol, magonol ursolic acid,ursic acid, morin, extract of sea buckthorn, a peroxide, an enzyme, aCamellia extract, a flavonoid, a flavan, halogenated diphenyl ether,creatine, and propolis. The application may be at least once a day,although up to five times per day may be preferred, and may be carriedout over a duration of time, e.g., one week, up to one year, up to threeyears or for a lifetime.

Various embodiments now will be described with reference to followingnon-limiting examples

EXAMPLES Example 1

A dentifrice composition having the formula of Table 1 was prepared. Thecompositions used in the Examples and Comparative Examples had varyingamounts of zinc oxide (varying from 0 to 2 wt %) and of amino acid(varying from 0 to 5 wt %). For Example 1 the dentifrice compositioncomprised 1 wt % zinc oxide powder, the ZnO being encapsulated, at a 50wt % loading, into a polymer film, in particular into a polymer filmcomprising a combination of two different molecular weight HPMCmaterials, comprising Methocel E5 and Methocel E50. The combined zincoxide/polymer film comprised 1 wt % ZnO and 1 wt % polymer film, eachweight being based on the total weight of the composition. For Example1, the dentifrice composition also comprised 4.3 wt % L-arginine

TABLE 1 Dentifrice Composition Ingredient % w/w Sorbitol Q.S. Water11.944 Silica -Zeodent 105 10.000 Silica - Zeodent 114 10.000Polyethylene Glycol 600 3.000 Silica - Zeodent 165 2.750 Source of Zincoxide (ZnO in polymer film) 0-2 Sodium Lauryl Sulfate 1.500Cocamidopropyl Betaine 1.250 Flavor 1.150 Titanium Dioxide 0.750 SodiumCMC - Type 7MF 0.650 Amino acid (L-arginine) 0-5 Sodium Saccharin 0.270Sodium Fluoride 0.243

To measure the deliver of zinc to hydroxyapatite, the dentifrice wasdiluted 1 part by weight dentifrice to 2 parts by weight water andstirred to disperse the dentifrice. Next a saliva coated hydroxyapatitedisk was added to this slurry. The disk was treated with the slurry for10 minutes and then rinsed three times with five mL of water. The diskwas then digested with nitric acid and total zinc measured by atomicabsorption spectroscopy.

The zinc uptake data from the dentifrice formula of Example 1 containingL-arginine and zinc oxide delivered from a polymer film when used as aslurry are provided in Table 2.

It may be seen from Example 1 that the zinc uptake was significant.

TABLE 2 Zinc uptake onto hydroxyapatite from a dentifrice slurry. Zincuptake Chelating molecule (ug/disk) Comparative Example 1 - None 14.1 ±1.1 Example 1 - L-arginine 103.5 ± 10.6

Comparative Example 1

For Comparative Example 1, the dentifrice composition having the formulaof Table 1 was prepared which comprised (like Example 1) 1 wt % ZnOencapsulated in a polymer film, but was modified as compared to Example1 in that no chelating molecule, such a L-arginine, was present.

The result is also shown in table 2. It may be seen from ComparativeExample 1 that the zinc uptake was significantly lower, nearly an orderof magnitude lower, than for Example 1.

A comparison of Example 1 and Comparative Example 1 shows that thechelating agent enhances delivery of the zinc oxide to the dentinsurface, in particular when employed in combination with a polymer film.

Examples 2 to 7 and Comparative Example 2

Example 1 was repeated except that for Example 2 a different amount ofL-arginine was used and for Examples 3 to 7 different amounts ofdifferent amino acids were used. In addition, for Examples 2 to 7 all ofthe formulas contained 1% ZnO as a powder, and no polymer film as forExample 1 was present. Examples 2 to 7 employed a 1.4:1 molar ratio ofthe respective amino acid to the ZnO powder. For Comparative Example 2,again no amino acid was present and the ZnO was present as a powder.

The results of the zinc uptake test as described above with respect toExample 1 are summarised in Table 3. The zinc uptake data fromdentifrice formula of Examples 2 to 7 containing zinc oxide powder and avariety of amino acids are shown in Table 3, as is the result fromComparative Example 2.

TABLE 3 Zinc uptake onto hydroxyapatite from a dentifrice slurry. Zincuptake Chelating molecule (ug/disk) Comparative Example 2 - None  5.9 ±0.4 Example 2 - L-arginine 99.0 ± 7.0 Example 3 - L-lysine 121. 5 ± 7.8 Example 4 - Serine 170.1 ± 8.0  Example 5 - Cysteine 188.8 ± 24.4Example 6 - Isoleucine 94.7 ± 2.0 Example 7 - Glutamic acid 95.3 ± 7.3

A comparison of Examples 1 and 2 in both Tables 2 and 3 confirms thatzinc uptake is significantly increased by the addition of to thedentifrice and the effect is observed whether the zinc oxide is added tothe dentifrice encapsulated in a polymer film (Example 1) or as a powder(Example 2). Table 3 highlights that zinc uptake can be increased by avariety of amino acids.

The results of these Examples and Comparative Examples demonstrate thatamino acids can improve delivery of insoluble zinc oxide to a surfacesimilar to that found in the oral cavity. The increased delivery of zincoxide should improve the antibacterial benefits associated with anincrease in zinc.

These Examples evidence a number of amino acids which appear to be ableto deliver zinc to surfaces in the oral cavity. Additional amino acidssuch as leucine, lysine, alanine, asparagine, aspartate, phenylalanine,glutamate, threonine, glutamine, tryptophan, glycine, valine, praline,tyrosine, and histidine could also be used. The delivery of other metaloxide particles, such as stannous or copper oxide, to surfaces in theoral cavity may also be improved by combination with amino acids.

Example 3

Example 3 was carried out to evaluate the occlusion efficacy of adentifrice formula including an amino acid as a chelator for zinc oxide.

For Example 3, a dentifrice composition having the formula of Table 1was prepared which comprised 1 wt % zinc oxide powder (as Example 2) and3 wt % of amino acid, which comprised L-arginine.

To evaluate the occlusion efficacy of the dentifrice formulas, dentindisks were prepared from human molars. The molars were sliced, sanded,and polished. Finally, the disks were etched with 6 wt % citric acid andsonicated to open the tubules on the dentin surface. Each disk wasbrushed for 1 minute and 30 seconds with a mechanical toothbrush and allby weight water to dentifrice slurry. After brushing, the disk wasrinsed for 15 seconds with water and then stored in a phosphate buffersolution for 15 minutes. This treatment cycle was repeated 7 times perdisk. After the seventh treatment, the disks were examined using aconfocal microscope to image the degree of surface coverage by thedentifrice product. The disks were then exposed to 1 min acid challenges(using a commercial cola carbonated beverage) and examined after eachtreatment to evaluate the amount of product remaining in the dentintubules. The results of this study are shown in FIG. 1.

It may be seen for Example 3 that after 7 brushing cycles there was goodocclusion of the dentin tubules. After 12 subsequent acid challengecycles using cola, there was still good occlusion of the dentin tubules.

Comparative Example 3

For Comparative Example 3, the dentifrice composition having the formulaof Example 3 (i.e. 1 wt % ZnO powder) but omitting the L-arginine wasprepared. This dentifrice was subjected to the same occlusion efficacytesting as Example 3, and the result is also shown in FIG. 1. It may beseen for Comparative Example 3 that after 7 brushing cycles there waspoor occlusion of the dentin tubules. After 12 subsequent acid challengecycles using cola, there was even worse occlusion of the dentin tubules.

A comparison of Example 3 and Comparative Example 3 shows that the metaloxide particles, in particular zinc oxide particles, provide good dentinocclusion when employed in combination with an amino acid such asL-arginine as a chelator.

Without being bound by any theory, it is believed that the amino acid islikely to improve the adhesion of ZnO inside dentin tubules, and toother surfaces in the oral cavity, by forming a bridge between zincoxide and the dentin. The negatively charged carboxylate group on theamino acid is suspected to bind to the zinc oxide (due to the existenceof a positive zeta potential at pH <9 for the zinc oxide, as disclosedin an article entitled “The effect of pH on the corrosion inhibition ofzinc pigments by phenol derivatives”, by at B. Muller and W. Klager,Corrosion Science, 38 (1996), pages, 1869-1875), with the positivelycharged group correspondingly binding to the surface of the dentin. Allamino acids are zwitterionic at physiological pH, and so it is believedthat the amino acid may be able to bind a charged particle to chargedsurfaces in the oral cavity. The charge and functionality of the R-groupof the amino acid varies among amino acids; however from the currentstudies by the inventors, the charge/functionality on the R-groupappears not to have a significant impact on zinc uptake tohydroxyapatite surfaces, as evidenced by the results of Table 3.

As shown in FIG. 1, it has been found by the present inventors that theincreased delivery of zinc oxide to dentin by L-arginine providesocclusion of dentin tubules which is more resistant to acid attack thanzinc oxide alone. This is an additional potential benefit provided bythe zinc oxide/amino acid system as occlusion of dentin tubules isassociated with hypersensitivity relief.

The invention claimed is:
 1. An oral care composition comprising: anorally acceptable vehicle; a source of metal oxide particles, whereinsaid metal oxide particles have a median particle size of from 1 to 7microns; one or more amino acids capable of chelating said metal oxideparticles selected from arginine, L-arginine, cysteine, leucine,isoleucine, lysine, L-lysine and serine, wherein the metal oxidecomprises zinc oxide; and further comprising a polymeric adherentmaterial, wherein the metal oxide is encapsulated in the polymericadherent material.
 2. The oral care composition according to claim 1wherein the metal oxide particles have a median particle size of 5microns or less.
 3. The oral care composition according to claim 1wherein the metal oxide particles have a particle size distribution of 3to 4 microns, a particle size distribution of 5 to 7 microns, a particlesize distribution of 3 to 5 microns, a particle size distribution of 2to 5 microns, or a particle size distribution of 2 to 4 microns.
 4. Theoral care composition according to claim 1 wherein the metal oxideparticles are present in an amount of up to 5% by weight, based on thetotal weight of the oral care composition.
 5. The oral care compositionaccording to claim 3 wherein the metal oxide particles are present in anamount of from 0.5 to 2% by weight, based on the total weight of theoral care composition.
 6. The oral care composition according to claim 1wherein the source of metal oxide particles is selected from a powder, ananoparticle solution; a nanoparticle suspension; a capsule; and a bead.7. The oral care composition according to claim 1 wherein at least oneof said one or more amino acids is L-arginine.
 8. The oral carecomposition according to claim 1 wherein at least one of said one ormore amino acids is present in an amount of up to 5% by weight, based onthe total weight of the oral care composition.
 9. The oral carecomposition according to claim 7 wherein at least one of said one ormore amino acids is present in an amount of from 0.5 to 5% by weight,based on the total weight of the oral care composition.
 10. The oralcare composition according to claim 8 wherein at least one of said oneor more amino acids is present in an amount of from 2.5 to 4.5% byweight, based on the total weight of the oral care composition.
 11. Theoral care composition according to claim 1 wherein the polymericadherent material comprises one or more cellulose polymers.
 12. The oralcare composition according to claim 11 wherein at least one of said oneor more cellulose polymers is a hydroxyalkyl cellulose polymer selectedfrom hydroxypropylmethyl cellulose (HPMC), hydroxyethylpropyl cellulose(HEPC), hydroxybutylmethyl cellulose (HBMC), and carboxymethyl cellulose(CMC).
 13. The oral care composition according to claim 12 wherein thepolymeric adherent material comprises a mixture of two hydroxyalkylcellulose polymers having different molecular weights and the metaloxide comprises zinc oxide which is encapsulated in the mixture of twohydroxyalkyl cellulose polymers.
 14. The oral care composition accordingto claim 1 wherein the polymeric adherent material comprises one or morepolymers selected from a poly (ethylene oxide) polymer,polyvinylpyrrolidone (PVP), polyethylene glycol (PEG)/polypropyleneglycol (PPG) copolymer, ethylene oxide (EO)-propylene oxide (PO) blockcopolymers, ester gum, shellac, pressure sensitive silicone adhesives,methacrylates, or mixtures thereof.
 15. The oral care compositionaccording to claim 1 which is a dentifrice composition.
 16. The oralcare composition according to claim 15, which is a toothpaste or a gel.17. The oral care composition according to claim 1, wherein thecomposition is formulated into a form selected from a mouth rinse, agum, a dissolvable lozenge, and a dissolvable film.
 18. A method ofreducing dental sensitivity comprising applying to the surface of amammalian tooth an oral care composition of claim
 1. 19. A method ofprotecting dental surfaces from acid-mediated degradation, comprisingapplying to the surface of a mammalian tooth an oral care composition ofclaim
 1. 20. A method of maintaining or increasing the systemic healthof a mammal comprising applying a composition to an oral surface of amammal at least once a day for a duration of time, wherein thecomposition comprises: a. an oral care composition of claim 1, and b. anagent selected from triclosan; triclosan monophosphate; chlorhexidine;alexidine; hexetidine; sanguinarine; benzalkonium chloride;salicylanilide; domiphen bromide; cetylpyridinium chloride (CPC);tetradecylpyridinium chloride (TPC); N-tetradecyl-4ethylpyridiniumchloride (TDEPC); octenidine; delmopinol; octapinol; nisin; zinc ionagent; copper ion agent; essential oils; furanones; bacteriocins,ethyllauroyl arginate, extracts of magnolia, a metal ion source,fluoride, stannous ions, arginine bicarbonate, honokiol, magonol,ursolic acid, ursic acid, morn, extract of sea buckthorn, a peroxide, anenzyme, a Camellia extract, a flavonoid, a flavan, halogenated diphenylether, creative, and propolis.
 21. A method of occluding a dentin tubulewithin the surface of a mammalian tooth comprising applying to the toothsurface a composition according to claim
 1. 22. An oral care compositionaccording to claim 1 and further comprising an agent selected fromtriclosan; triclosan monophosphate; chlorhexidine; alexidine;hexetidine; sanguinarine; benzalkonium chloride; salicylanilide;domiphen bromide; cetylpyridinium chloride (CPC); tetradecylpyridiniumchloride (TPC); N-tetradecyl-4ethylpyridinium chloride (TDEPC);octenidine; delmopinol; octapinol; nisin; zinc ion agent; copper ionagent; essential oils; furanones; bacteriocins, ethyllauroyl arginate,extracts of magnolia, a metal ion source, fluoride, stannous ions,arginine bicarbonate, honokiol, magonol, ursolic acid, ursic acid, morn,extract of sea buckthorn, a peroxide, an enzyme, a Camellia extract, aflavonoid, a flavan, halogenated diphenyl ether, creative, and propolis,for use in a method of maintaining or increasing the systemic health ofa mammal.
 23. The oral care composition according to claim 13 whereinthe metal oxide particles are present in an amount of from 0.5 to 2% byweight, based on the total weight of the oral care composition.
 24. Theoral care composition according to claim 23 wherein at least one of saidone or more amino acids is present in an amount of from 0.5 to 5% byweight, based on the total weight of the oral care composition.
 25. Theoral care composition according to claim 24 wherein at least one of saidone or more amino acids is L-arginine.
 26. The oral care composition ofclaim 1, further comprising stannous fluoride.